Stochastic electrotransport selectively enhances the transport of highly electromobile molecules

Proc Natl Acad Sci U S A. 2015 Nov 17;112(46):E6274-83. doi: 10.1073/pnas.1510133112. Epub 2015 Nov 2.

Abstract

Nondestructive chemical processing of porous samples such as fixed biological tissues typically relies on molecular diffusion. Diffusion into a porous structure is a slow process that significantly delays completion of chemical processing. Here, we present a novel electrokinetic method termed stochastic electrotransport for rapid nondestructive processing of porous samples. This method uses a rotational electric field to selectively disperse highly electromobile molecules throughout a porous sample without displacing the low-electromobility molecules that constitute the sample. Using computational models, we show that stochastic electrotransport can rapidly disperse electromobile molecules in a porous medium. We apply this method to completely clear mouse organs within 1-3 days and to stain them with nuclear dyes, proteins, and antibodies within 1 day. Our results demonstrate the potential of stochastic electrotransport to process large and dense tissue samples that were previously infeasible in time when relying on diffusion.

Keywords: CLARITY; molecular transport; stochastic electrotransport; tissue clearing; tissue labeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies / chemistry*
  • Coloring Agents* / chemistry
  • Coloring Agents* / pharmacokinetics
  • Electrochemical Techniques
  • Mice
  • Models, Biological*
  • Models, Chemical*
  • Porosity

Substances

  • Antibodies
  • Coloring Agents